tbuckley/cabot-search huggingface dataset:
AB0150 CIRCULARRNA AS A POTENTIAL BIOMARKER OF GRANULOMATOSIS WITH POLYANGIITIS
Authors: S. Lichołai, K. Wójcik, K. Wawrzycka-Adamczyk, M. Surmiak, M. Korkosz, J. Musiał
Journal: Annals of the Rheumatic Diseases (2022)

Background Granulomatosis with polyangiitis (GPA) belong to ANCA-associated vasculitides, a heterogeneous group of disorders whose clinical presentation ranges from isolated lesions affecting a single organ to life-threatening conditions. The etiology of the disease is not fully understood, and there is a lack of reliable and unambiguous diagnostic and prognostic markers. Research in recent years points to the potential use of circulating free nucleic acids as a potential biomarkers in human pathology. Circular RNAs (circRNAs) belong to the group of non-coding RNAs, a group of potentially regulatory RNAs generated by linkage between a downstream 3′ splice site and an upstream 5′ splice site in a process known as backsplicing. CircRNAs were found in in nearly all tissues and recently have been reported to regulate gene expression by sponging miRNA. However their role in specific human conditions is largely unknown. Objectives The aim of our study was to assess the potential role of circRNA in diagnosis and monitoring of GPA. Methods CircRNAs were selected using bioinformatic analysis of RNA-seq data. Serum samples were obtained from 30 patients with GPA and 30 healthy controls. Levels of circRNA weres assessed using qPCR with specific primers and probes. Statistical analysis was performed using dedicated packages for R and R Studio software. Results Levels of at least 10 serum circRNAs distinguished GPA patients from controls and 6 of them reached statistical significance. There was also an apparent difference in the levels of selected molecules between GPA exacerbation and remission (hsa_circ_0015167 – RQ 5.97, p&lt;0.05; hsa_circ_0045266 – RQ 4.53, p&lt;0.05). CircRNAs that differentiate patients from healthy individuals were associated with genes for P-selectin, VCAM and interleukins, among others. In contrast, molecules derived from catherins do not differentiate between the study and control groups. Conclusion Our results suggest that circRNA could be potentially used as a biomarker facilitating GPA diagnosis. Moreover, the observed differences depending on the stage of the disease could allow for monitoring the disease and predicting its progression. The association of molecules which levels differ between the test and control groups with genes previously associated with the development of the disease strongly suggests their potential involvement in its pathogenesis, which in turn strengthens the diagnostic specificity of the proposed markers. Acknowledgements This research was supported by National Center of Science, grant number 2018/31/B/NZ6/03898. Disclosure of Interests None declared
Maternal antenatal vitamin D supplementation and offspring risk of atopic eczema in the first 4 years of life: evidence from a randomized controlled trial
Authors: Sarah El-Heis, Stefania D’Angelo, Elizabeth M. Curtis, Eugene Healy, Rebecca J. Moon, Sarah R. Crozier, Hazel Inskip, Cyrus Cooper, Nicholas C. Harvey, Keith M. Godfrey
Journal: British Journal of Dermatology (2022)

Summary Background Evidence linking prenatal maternal vitamin D supplementation with the offspring’s risk of atopic eczema is inconsistent, with most data coming from observational studies. Objectives To examine the influence of maternal cholecalciferol supplementation during pregnancy on the risk of atopic eczema in the offspring at ages 12, 24 and 48 months. Methods Within the UK Maternal Vitamin D Osteoporosis Study (MAVIDOS) double-blind, randomized placebo-controlled trial, we examined the relationship of maternal vitamin D supplementation during pregnancy with offspring atopic eczema at ages 12, 24 and 48 months. In MAVIDOS, pregnant women were allocated to either cholecalciferol 1000 IU per day or matched placebo, taken from around 14 weeks’ gestation until delivery, with the primary outcome of neonatal whole-body bone mineral content. The prevalence of atopic eczema in the offspring was ascertained at ages 12 (n = 635), 24 (n = 610) and 48 (n = 449) months, based on the UK Working Party criteria for the definition of atopic dermatitis. The trial was registered with ISRCTN (82927713) and EudraCT (2007-001716-23). Results The characteristics of mothers and offspring were similar between the intervention and placebo groups, apart from longer breastfeeding duration in the intervention group. Adjusting for breastfeeding duration, offspring of mothers who received cholecalciferol 1000 IU daily had a lower odds ratio (OR) of atopic eczema at age 12 months [OR 0·55, 95% confidence interval (CI) 0·32–0·97, P = 0·04]; this effect weakened and was not statistically significant at ages 24 months (OR 0·76, 95% CI 0·47–1·23) or 48 months (OR 0·75, 95% CI 0·37–1·52). The statistical interaction of intervention and breastfeeding duration in relation to eczema at age 12 months was not significant (P = 0·41), but stratification showed reduced infantile eczema risk in the intervention group for infants breastfed for ≥ 1 month (OR 0·48, 95% CI 0·24–0·94, P = 0·03) but not in those breastfed for &amp;lt; 1 month (OR 0·80, 95% CI 0·29–2·17, P = 0·66). Conclusions Our data provide the first randomized controlled trial evidence of a protective effect of antenatal cholecalciferol supplementation on the risk of infantile atopic eczema, with the effect potentially being via increased breast milk cholecalciferol levels. The findings support a developmental influence on atopic eczema, and point to a potentially modifiable perinatal influence on atopic eczema. What is already known about this topic? There are currently no antenatal interventions proven to reduce the incidence of infantile atopic eczema in the general population.However, observational studies have led to speculation that antenatal vitamin D supplementation may be beneficial.
AB0719 ECONOMIC BURDEN IN SCLERODERMA
Authors: L. Martin Calderon, M. Chaudhary, J. Pope
Journal: Annals of the Rheumatic Diseases (2022)

Background Scleroderma (SSc) is a multi-system autoimmune disease, characterized by vasculopathy and fibrosis of the skin and internal organs, associated with substantial morbidity and disability. Patients with SSc commonly require considerable healthcare resources resulting in significant economic impact. Objectives The purpose of this systematic review is to provide a narrative summary of the economic impact and healthcare resource utilization associated with SSc. Methods MEDLINE and EMBASE were searched without language restriction from inception to January 20 th , 2021. Studies were included if they provided information regarding total, direct, and indirect medical costs including medication, diagnostic test, and assistive devices costs. The cost of SSc complications was additionally collected. Included observational studies had risk of bias assessments through the Joanna Briggs Institute cross-sectional and case series checklists, and the Newcastle-Ottawa Cohort and Case-Control study scales. Results The search retrieved 1777 studies, of which 33 were included representing 20 cross-sectional, 10 cohort, and 3 case-control studies. Studies used various methods of calculating cost including prevalence-based cost-of-illness approach, bottom-up cost analysis, humanistic approach, and health resource units cost analyses. Overall scleroderma total annual medical cost ranged from USD $14,959-$23,268 in USA, CAD$10,673-$18,453 in Canada, €4,607-€30,797 in Europe, and AUD $7,060 to $11,607 in Oceania. Annual cost for SSc associated with interstitial lung disease and pulmonary arterial hypertension was USD $31,285-$55,446 and $44,454-$63,320, respectively. Conclusion Globally, SSc represents high patient and systemic economic burden. SSc-associated complications increase economic burden and are variable depending on geographical location, and access. References [1]López-Bastida J, Linertová R, Oliva-Moreno J, Serrano-Aguilar P, Posada-de-la-Paz M, Kanavos P, et al. Social/economic costs and health-related quality of life in patients with scleroderma in Europe. The European Journal of Health Economics. 2016 Apr;17(1):109-17. [2]Morrisroe K, Stevens W, Sahhar J, Ngian GS, Ferdowsi N, Hill CL, et al. Digital ulcers in systemic sclerosis: their epidemiology, clinical characteristics, and associated clinical and economic burden. Arthritis research &amp; therapy. 2019 Dec;21(1):1-2. Disclosure of Interests None declared
POS0990 Deep learning algorithms for magnetic resonance imaging of inflammatory sacroiliitis in axial spondyloarthritis.
Authors: H. Y. Chung, C. W. S. Chan
Journal: Annals of the Rheumatic Diseases (2022)

Background Magnetic resonance imaging (MRI) of the sacroiliac (SI) joints is increasingly important in the management of axial spondyloarthritis (SpA). Artificial intelligence (AI) may be the next crucial step in enabling the widespread application of MRI. Objectives To develop a deep learning algorithm for detection of active inflammatory sacroiliitis in short tau inversion recovery (STIR) sequence MRI. Methods A total of 326 participants with axial spondyloarthritis (SpA), and 63 participants with non-specific back pain (NSBP) were recruited. STIR MRI of the SI joints was performed and clinical data were collected. Region of interests (ROIs) were drawn outlining bone marrow edema, a reliable marker of active inflammation, which formed the ground truth masks from which “fake-colour” images were derived. Both the original and “fake-colour” images were randomly allocated into either the training and validation dataset or the testing dataset. Attention U-net was used for the development of deep learning algorithms. As comparison, an independent radiologist and rheumatologist blinded to the ground truth masks, were tasked with identifying bone marrow edema in the MR images. Results Inflammatory sacroiliitis were identified in 1398 MR images from 228 participants. No inflammation was found in 3944 MR images from 161 participants. The mean sensitivity of algorithms derived from the original dataset and “fake-colour” image dataset were 0.86±0.02, and 0.90±0.01 respectively. The mean specificity of algorithms derived from the original and “fake-colour” image dataset were 0.92±0.02, and 0.93±0.01 respectively. The mean testing dice coefficients were 0.48± 0.27 for the original dataset and 0.51±0.25 for the “fake-colour” image dataset. The area under the curve of the receiver operating characteristic (AUC-ROC) curve of the algorithms using original dataset and “fake-colour” image dataset were 0.92 and 0.96 respectively. Sensitivity and specificity of algorithms were comparable to interpretation by a radiologist, but outperformed the rheumatologist. Conclusion An MRI deep learning algorithm was developed for detection of inflammatory sacroiliitis in axial SpA. Disclosure of Interests None declared
AB1391 19% PATIENTS WITH CHRONIC RHEUMATIC INFLAMMATORY DISEASES PRESENT AN UNFAVORABLE PREGNANCY OUTCOME: A DESCRIPTIVE ANALYSIS OF THE NATIONAL FRENCH SOCIAL SECURITY DATABASE
Authors: A. Moltó, A. Ajrouche, D. Tran, B. Roux, N. Costedoat-Chalumeau, E. Elefant, V. Tsatsaris, J. Fresson, B. Bader-Meunier, B. Fautrel, F. Tubach
Journal: Annals of the Rheumatic Diseases (2022)

Background patients with chronic rheumatic inflammatory diseases (CRID, i.e. rheumatoid arthritis (RA) or spondyloarthritis (SpA)) have been reported to have poorer pregnancy outcomes than the general population. Objectives to describe the pregnancy outcomes of singleton in patients with CRID in France in the past decade. Methods this is an analysis of the French Health Insurance claims database (SNDS), which represents 87% of the French population) from 2008 to 2016. To be included in the analysis patients had to be identified as RA or SpA according to existing diagnostic algorithms, to have at least one pregnancy declaration in the database, and to have continuous health insurance from 1-year before pregnancy onset to 1-year after end of the pregnancy or until death (if death occured before the 1-year-period after the end of pregnancy) to be included. Only the first singleton pregnancy occurring during the study period was included in this analysis. Both maternal and pregnancy outcomes were considered. Outcomes were identified either by ICM-10 codes or hospital discharge summaries discharge between 2008-2016. Results Among the 35 737 identified adult females with a CRID diagnosis (40.7% with RA and 59.3% with SpA), 27 722 (78%) had a pregnancy during the study period. 11 274 (42%) had received at least one DMARD prior to the pregnancy and were included in the analysis. Among them, only 4025 (36%) were exposed to DMARDs during pregnancy. Mean (SD) age of females at the start of the pregnancy was 32 (5) years, and mean (SD) disease duration was 4 (4) years. Pregnancy ended before 13 WG in 21% and after 37 WG in 70% cases. Live-birth represented the most frequent pregnancy outcome (76.9%), and overall 34.7% patients presented at least one unfavorable outcome (see Table 1). Table 1. Unfavourable outcome N(% ) Pregnancy outcomes Miscarriage (&lt;22WG ) 579 (5.3%) Abortion 91 (0.8%) Stillbirth 48 (0.4%) Preterm delivery (&gt;= 22WG and &lt;37 WG ) 779 (7.1%) Low weight at birth (&lt;3th percentile ) 287 (2.6%) Perinatal mortality (22WG to 6 days of life ) 2 (0%) Maternal outcomes Severe maternal infection* 211 (1.9%) Newborn outcomes Hospitalisation in neonatal intensive care &gt; 48h in full-term newborns (after 37 WG ) 95 (0.8%) Neonatal mortality (27 first days of life ) 2 (0%) Severe infection * during first year 603 (5.3%) Conclusion More than 75% pregnancies in patients with CRID resulted in a live-birth. Prevalence of miscarriage was surprisingly low, probably related to under-coding. Maternal and infant outcomes seemed comparable to general population. Whether medications had an impact on such outcomes is currently under evaluation. Disclosure of Interests None declared
AB0160 THE RELATIONSHIP BETWEEN THE LEVEL OF FETUIN-A AND LABORATORY MARKERS OF CONNECTIVE TISSUE DESTRUCTION IN PATIENTS WITH RHEUMATOID ARTHRITIS
Authors: Y. Akhverdyan, В. Zavodovsky, E. Papichev, J. Polyakova, L. Seewordova
Journal: Annals of the Rheumatic Diseases (2022)

Background It is known that there are biochemical markers of cartilage and bone tissue destruction, which reflect the metabolic processes occurring in tissues. For example, in rheumatoid arthritis (RA), routine markers such as CTX-I, a bone degradation marker (C-terminal telopeptide of type I collagen) and CTX-II, a cartilage degradation marker (C-terminal telopeptide of type II collagen), can be used. Also, to assess the state of cartilage tissue, the determination of type II collagen fragments by Urine CartiLaps is widely used, which allows not only primary diagnosis, but also dynamic monitoring of metabolic processes. Objectives The aim of our research was to study the relationship between the level of fetuin-A (FeA) and laboratory markers of bone and cartilage tissue degradation in the blood serum of patients with RA. Methods We observed 110 patients with a verified diagnosis of RA, the control group consisted of 30 practically healthy individuals without joint diseases. The group of patients with RA and the control group were comparable in terms of age (p=0.083), gender (p=0.116), BMI (p=0.302). The diagnosis of RA was based on the clinical classification adopted at the EULAR/ACR in 2010. The level of FeA in the blood serum was determined once by enzyme immunoassay using commercial test systems (Human Fetuin-A ELISA Biovender Cat No. 191-0371). Results We have assessed the FeA level in the group of RA patients and healthy donors. The normal level of FA in healthy individuals, calculated as M±2σ, ranged from 653.55 µg/ml to 972.19 µg/ml. FeA level was normally distributed (K-S d=0.062, p&gt;0.2). We also studied the relationship between indicators of bone metabolism and the concentration of FeA. In patients with normal FeA levels (n=87), the mean CTX-1 level was 35 ng/mL; in patients with reduced FeA levels (n=23), the mean CTX-1 level was 51 ng/ml (t=-2.42 p =0.016). Thus, with a decrease in the FeA level, CTX-I (an indicator of osteodestruction) tended to increase. Next, we analyzed the relationship between low and normal levels of FeA and the Cartilaps/urine creatinine ratio using intragroup analysis methods. In the group with low FeA level Cartilaps/urinary creatinine was 598.9±223.72 µg/mmol versus 481.17±226.93 µg/mmol in the group with normal FeA level (Z=-2.311; p=0.021). Our data probably allow us to associate the FeA level with the rate of cartilage tissue destruction. Conclusion Considering that the levels of laboratory markers of cartilage and bone collagen degradation Cartilaps and CTX-I were statistically lower in the presence of an elevated serum level of FeA, we can conclude that FeA has chondro- and osteoprotective properties. It can also be assumed that the level of this marker can be used to predict the rate of cartilage destruction in patients with RA, but this issue requires further study. Disclosure of Interests None declared
LAG3 ectodomain structure reveals functional interfaces for ligand and antibody recognition
Authors: Qianqian Ming, Daiana P. Celias, Chao Wu, Aidan R. Cole, Srishti Singh, Charlotte Mason, Shen Dong, Timothy H. Tran, Gaya K. Amarasinghe, Brian Ruffell, Vincent C. Luca
Journal: Nature Immunology (2022)
AB1173 INCIDENT CASES OF COVID-19 AND VACCINATION ADHERENCE IN A MULTICENTRIC COHORT OF INFLAMMATORY ARTHRITIS IN BRAZIL
Authors: S. M M de Souza, A. C. Medeiros-Ribeiro, M. Bredemeier, A. Duarte, M. Pinheiro, B. Stadler, J. C. Macieira, R. Ranza, J. Miranda, V. Valim, G. Castro, M. Bertolo, M. D. F. Sauma, V. Fernandes, R. Botelho, C. Brenol, H. M. Da Silveira DE Carvalho, S. Studart, G. Da Rocha Castelar Pinheiro, L. Rocha, H. De Leon de Lima, I. Pereira, M. Ohira Gazzeta, A. Kakehasi, P. Louzada, A. L. S. Hayata, F. Pina, M. Alves Ferreira, L. Balarini, I. G. Silveira, S. Kowalski, D. Titton, R. Mendonça Da Silva Chakr, A. Ranzolin, I. Laurindo, R. Xavier
Journal: Annals of the Rheumatic Diseases (2022)

Background The SARS-CoV-2 virus has caused a worldwide health crisis. Patients with inflammatory arthritis are at higher risk of hospitalization and death by COVID-19 due to comorbidities or immunosuppressive treatments. Vaccination is one the most important strategies to control the pandemic. Objectives To evaluate the incident cases of SARS-CoV-2 infection in a multicentric cohort of inflammatory arthritis in Brazil. Methods BiobadaBrasil is a multicentric registry-based cohort study of Brazilian patients with rheumatic diseases starting their first bDMARD or tsDMARD (1). The present analysis is a retrospective evaluation of adult patients with inflammatory arthritis (rheumatoid arthritis – RA, spondylarthritis -SpA and psoriatic arthritis-PsA) that were alive since the beginning of the COVID-19 pandemics in Brazil in February 2020. We evaluated the incidence and severity of COVID-19 infection and the adherence to anti- SARS-CoV-2 vaccines schedules, up to January 2022. Results A total of 300 patients were interviewed and 69 (23.0%) reported confirmed anti-SARS-CoV infection and 5 (1.7%) had a second infection. Among known infected patients, 18.8% need hospitalization and oxygen support, 7.2% were admitted at ICU, and 5.8% died. After COVID-19 infection, 31.8% reported worsening of disease activity but only 6.1% had modification in medication due to disease activity. Distribution of cases followed the pattern of waves observed in Brazil (Figure 1). Regarding vaccination, 285 (95%) reported to have received at least one dose of any anti-SARS-CoV-2 vaccine: 43% received the first with the adenovirus ChAdOx1 nCoV-19 (AstraZeneca) adenovirus vaccine, 32% received the Sinovac-CoronaVac inactivated vaccine, 22% received the BNT162b2 (Pfizer-BioNtech) mRNA vaccine and 3% received the BNT162b2 (Pfizer-BioNtech) adenovirus vaccine. Almost all (98.1%) of these patients had already received the second dose of vaccine and after the first and second vaccine doses, 6% and 4% of patients, respectively, reported worsening of articular disease activity, while, after the third dose, no patient reported disease activity worsening. Figure 1. Conclusion During the pandemics, patients with inflammatory arthritis had a pattern of distribution of cases very similar to general population. Adherence to vaccination is high and well tolerated. References [1]Bredemeier et al. J Rheumatol 2021;48:1519-27 Disclosure of Interests None declared
Tissue-resident memory CD8+ T cells possess unique transcriptional, epigenetic and functional adaptations to different tissue environments
Authors: John T. Crowl, Maximilian Heeg, Amir Ferry, J. Justin Milner, Kyla D. Omilusik, Clara Toma, Zhaoren He, John T. Chang, Ananda W. Goldrath
Journal: Nature Immunology (2022)
POS1185 PERFORMANCE OF ADENOSIN DEAMINASE ACTIVITY IN SYNOVIAL FLUID FOR THE EARLY DIAGNOSIS OF TUBERCULOUS ARTHRITIS: A META-ANALYSIS
Authors: J. Ena, J. C. Cortés-Quiroz, J. A. Bernal, A. Pons, J. M. Senabre-Gallego, G. Santos Soler, C. Raya-Santos, J. Rosas
Journal: Annals of the Rheumatic Diseases (2022)

Background Adenosin deaminase activity (ADA) has shown good performance in diagnosing pleural, peritoneal and meningeal tuberculosis. Still, the performance of ADA activity in synovial fluid for the diagnosis of tuberculous arthritis has received less attention. Objectives To analyze the performance of ADA in synovial fluid to diagnosis tuberculous artrhritis. Methods We research Medline and EMBASE from the inception to October 2021 and the American College of Rheumatology and European League Against Rheumatism for conference abstracts (2012-2021) to assess the accuracy of ADA activity in synovial fluid compared to a composite reference standard (necrotizing granulomas in a synovial biopsy; acid-fast stain, Mycobacterium culture or RT-PCR assay for tuberculosis and/or clinical response to tuberculosis treatment) to early diagnosis tuberculous arthritis. We performed meta-analysis using a random-effects model and evaluated the sources of heterogeneity via subgroup analysis and meta-regression. Results Seven independent studies (N= 307 subjects) that compared ADA activity in synovial fluid with the composite reference standard were included. The pooled sensitivity and specificity of ADA activity was 0.939 (95% confidence Interval [CI], 0,873-0,977; heterogeneity p=0.297; I2=17.4%) and 0.885 (95% confidence Interval [CI], 0.833-0.925; heterogeneity p=0.002; I2=85.3%) compared to the composite reference standard, respectively. The random-effects model for pooled diagnostic Odds Ratio was 74.582 (95% CI, 19.826-280.57; heterogeneity p=0.133; I2=38.8%). The receiver operating characteristic curve area was 0.9617 (95% CI, 0.925-1.000). Meta-regression did not identify the type of study (prospective or retrospective), country of publication, type de assay, or cut-off value as sources of heterogeneity. Conclusion Measuring adenosine deaminase activity in synovial fluid demonstrates good performance for the early diagnosis joint tuberculosis. Acknowledgements El estudio fue apoyado con una beca de investigación de la Asociación para la Investigación en Reumatología de la Marina Baixa (AIRE-MB) Disclosure of Interests None declared